Page 272 - Review of Medical Microbiology and Immunology ( PDFDrive )

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mebooksfree.com mebooksfree.com Virus A mebooksfree.com B Antiviral infection CHAPTER 33 Host Defenses 261 mebooksfree.com
Interferon
Viral mRNA
molecules
proteins
Viral

C
FIGURE 33–1
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Induction and action of interferon. A: Virus infection induces the synthesis of interferon, which then leaves the infected
cell. B: Interferon binds to the surface receptor of an uninfected cell and induces the synthesis of three new cell-encoded enzymes (antiviral
proteins). C: A new virion enters the cell, but viral replication is inhibited by the interferon-induced antiviral proteins. One of these antiviral pro-
teins is a ribonuclease that degrades mRNA, and another is a protein kinase that phosphorylates an initiation factor that inhibits protein synthe-
sis. (Tortora G, Microbiology: An Introduction. 1st edition, © 1982. Reprinted by permission of Pearson Education Inc, New York, New York. )

This extensive list of inducers makes it clear that
Interferon
induction of these interferons is not specific. Similarly,
Binds to
their inhibitory action is not specific for any particular
cell surface
virus. However, they are typically specific in regard to
the host species in which they act (i.e., interferons pro-
duced by human cells are active in human cells but are Uninfected cell produces
inactive oligo A synthetase,
ribonuclease, and protein kinase
much less effective in cells of other species). It is clear,
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Active RNAse mebooksfree.com
therefore, that other animals cannot be used as a source
of interferons for human therapy. Rather, the genes for
Virus infection
produces
human interferons have been cloned, and interferon for
dsRNA
medical use is now produced by genetic engineering
Inactive
techniques.
Inactive
Inactive
oligo A
ribonuclease
synthetase
Action of Alpha & Beta Interferons
ds
ds
RNA
RNA
Interferons inhibit the intracellular replication of a wide
Active
variety of DNA and RNA viruses but have little effect on
protein kinase
the metabolism of normal cells. The selectivity arises from
the presence of double-stranded RNA in virus-infected
cells, which is not present in uninfected cells. Oligo A degrades initiation factor-2
Phosphorylates
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mRNA
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Interferons have no effect on extracellular virus parti-
cles. Interferons act by binding to a receptor on the cell
surface that signals the cell to synthesize three proteins,
Inhibits
thereby inducing the “antiviral state” (Figure 33–2). These
three proteins are inactive precursor proteins until they are
activated by double-stranded RNA synthesized during viral
replication. As a result, these proteins are active in virus-
infected cells but not in uninfected cells.
Death of
The three cellular proteins are (1) a 2,5-oligo A synthe-
virus-infected cell
tase that synthesizes an adenine trinucleotide (2,5-oligo A),
(2) a ribonuclease that is activated by 2,5-oligo A and
degrades viral and cellular mRNAs, and (3) a protein
uninfected cell. Interferon binds to the surface of the uninfected cell
and induces three proteins that remain inactive until a virus infects the
kinase that phosphorylates an initiation factor (eIF-2) for FIGURE 33–2 Interferon induces an antiviral state within an
cell. These proteins are oligo A synthetase, ribonuclease, and protein
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protein synthesis, thereby inactivating it. The end result is
kinase. When a virus infects that cell, a double-stranded RNA (dsRNA) is
that both viral and cellular protein synthesis is inhibited
synthesized as part of the viral replicative cycle. The dsRNA activates
and the infected cell dies. No virus is produced by that cell,
and the spread of the virus is reduced.
ribonuclease to degrade viral (and cell) mRNA. The dsRNA also acti-
Because interferons are produced within a few hours of
vates the protein kinase that phosphorylates initiation factor-2 (eIF-2).
the initiation of viral replication, they act in the early phase
This inhibits both viral and cell protein synthesis. The cell dies without
of viral diseases to limit the spread of virus. In contrast,
producing progeny virus, thereby limiting the spread of infection.
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